title: X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.
abstract: The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Larschan
authors.forename: Eric P
authors.initials: EP
authors.lastname: Bishop
authors.forename: Peter V
authors.initials: PV
authors.lastname: Kharchenko
authors.forename: Leighton J
authors.initials: LJ
authors.lastname: Core
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: Mitzi I
authors.initials: MI
authors.lastname: Kuroda
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D059006:Chromosomes, Insect / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D017344:Genes, Insect / Q000235:genetics; D050172:Genes, X-Linked / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; C094166:msl-2 protein, Drosophila; D012319:RNA Polymerase II